Feed-forward inhibitory circuits are a major source of synaptic inhibition to cortical neurons. The specific means by which they control the activity of cortical neurons is, however, poorly understood. The goal of this proposal is to address the mechanism by which feed-forward inhibitory circuits activated by thalamic afferents control the excitability of cortical neurons. We will test the hypothesis that thalamo-cortical feed-forward inhibition reduces the integration time window of cortical neurons, and enforces temporal fidelity of signal transmission between the thalamus and the cortex. This proposal has two aims: Aim 1 addresses the role of thalamo-cortical feed-forward inhibition in controlling the integration time window and spike timing of cortical neurons. Aim 2 addresses the cellular mechanism of thalamo-cortical feed-forward inhibition. The experiments will be performed on acute mouse thalamo-cortical slices using electrophysiological and morphological techniques. This study will provide insight into the functional role of feed-forward inhibition and the mechanisms by which neuronal networks balance excitation with synaptic inhibition. A deeper understanding of the mechanisms that control cortical excitability may contribute to the development of therapies aimed at preventing epileptogenesis in cortical areas.